Models of virus-induced demyelination have been of great interest to investigators concerned with Multiple Sclerosis. We have been studying the murine Theiler's model of virus-induced demyelination, in which data strongly suggest an immunopathologic mechanism of myelin degeneration. The identification of additional animal models in which similar mechanisms might be operating would be important as it would suggest that demyelination by combined viral-immunologic attack may represent a more general pattern of virus-CNS interaction. The general objective of this project is that of further characterizing the Theiler's model my morphological and immunopathologic techniques and to add two further models of virus-induced demyelination in which immunopathologic mechanisms are suggested. Specific aims are as follows: (1) Ultrastructural studies of different mouse strains with special emphasis on the C3H strain in which conspicuous Schwann cell participation is observed during remyelination. (2) Ultrastructural studies of mice infected with cell cultured adapted Theiler's viruses TO4 and WW. These viruses produce a slower disease with apparent clinical sparing of grey matter and striking Schwann cell remyelination of CNS white matter. (3) Ultrastructural and autoradiographic studies of the remyelinating phase of Theiler's infection with special emphasis on Schwann cell mechanisms of remyelination in CNS and Schwann cell origin. (4) Studies of demyelination in two new infections produced by a temperature-sensitive (ts) mutant of Vesicular Stomatitis Virus (VSV), tsG41, and a ts mutant of the human isolate Chandipura virus (CV) ts472. (5) Immunosuppression and adoptive immunization experiments with all three models to better characterize immunemediated demyelination. (6) Light and ultrastructural immunoperoxidase studies aimed at (a) visualizing viral antigen in relation to demyelinating lesions, (b) localizing antiviral and/or antimyelin antibody in diseased white matter. (7) Studies of the host-immune response both serum and cell-mediated to both viral antigens and myelin basic protein. With such studies, we hope to more clearly establish these models as representative of virus induced immune-mediated demyelination, and in addition to increase our understanding of the complex process of CNS myelin repair.